PatientID: 4

KindredID: 4

Case: F, 24Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: Family history involved.

CasePresentingHPOs: HP:0010797; HP:0009711 (hemangioblastoma, retinal capillary hemangioma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.F75Yfs*57 (c.222_223insT)

CaseProblemVariantFreeText: paper states 2 mismatched protein changes vs cDNA changes: c.223_224insT matches with p.F76Lfs*56. To get the given protein sequence they use: p.I75fs, the mutation should be c.222_223insT.

LegacyVariant: N/A

ClinVar: N/A

CAID: CA2499306953 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2499306953

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_1_frameshift_variant

CivicName: F76Lfs*56 (c.224dup)

MultipleGeneVariants: N/A

PatientID: 66

KindredID: 66

Case: Sex, Age, Ethnicity unknown

DiseaseAssertion: VHL (asymptomatic)

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0030421; HP:0009711; HP:0030405; HP:0006770; HP:0100634; HP:0010797 (epididymal tumour, retinal capillary hemangioma, pancreatic endocrine tumour, clear cell renal cell carcinoma, neuroendocrine neoplasm, hemangioblastoma)

CaseNotHPOFreeText: patient was not recorded to have an epididymal tumor, a pancreatic endocrine tumour (pancreatic neuroendocrine neoplasm), CCRCC, a neuroendocrine neoplasm (pheochromocytoma/paraganglioma), nor a CNS hemangioblamstoma.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes; see table S1 for VHL subject genetic and manifestation information.

Variant: p.F136Lfs*23 (c.408delT)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 43601 https://www.ncbi.nlm.nih.gov/clinvar/variation/43601/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: F136Lfs*23 (c.408delT)

MultipleGeneVariants: N/A

PatientID: 46

KindredID: 46 **

Case: Sex, Age, Ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: ** Patients 46, 50, 71, and 72 were reported previously in Aronoff et al, 2018 (PMID: 29437867) as family 5

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: CNS hemangioblamstoma

CaseNotHPOs: HP:0030421; HP:0009711; HP:0030405; HP:0006770; HP:0100634 (epididymal tumour, retinal capillary hemangioma, pancreatic endocrine tumour, clear cell renal cell carcinoma, neuroendocrine neoplasm)

CaseNotHPOFreeText: patient was not recorded to have an epididymal tumor, a pancreatic endocrine tumour (pancreatic neuroendocrine neoplasm), CCRCC, nor a neuroendocrine neoplasm (pheochromocytoma/paraganglioma)

CasePreviousTesting: N/A

PreviouslyPublished: 29437867

SupplementalData: Yes; see table S1 for VHL subject genetic and manifestation information.

Variant: p.F136Lfs*23 (c.408delT)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 43601 https://www.ncbi.nlm.nih.gov/clinvar/variation/43601/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: F136Lfs*23 (c.408delT)

MultipleGeneVariants: N/A

GroupID/ KindredID: 4414NCI, 4577NCI

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the National Cancer Institute database, with an unknown number of members belonging to two family IDs: Family 4414NCI and 4577NCI. Table 4 lists all ID and mutations associated with individuals with pheochromocytoma.

GroupPresentingHPOs: HP:0002666 (pheochromocytoma)

GroupHPOFreeText: Described as 2 VHL families with pheochromocytoma. Other phenotypes are likely, including renal cell carcinoma, however not detailed here.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.F119L (c.357C>G)

LegacyVariant: p.F119L (c.570C>G)

CaseProblemVariantFreeText: N/A

ClinVarID: 625240 https://www.ncbi.nlm.nih.gov/clinvar/variation/625240/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: F119L (c.357C>G)

MultipleGeneVariants: N/A

PatientID: 8

KindredID: 5

Case: M, 5Y0M, Ethnicity Unknown

DiseaseAssertion: Asymptomatic

FamilyInfo: Positive. The patient's mother (5) and aunt (4) were confirmed to have the mutation and had VHL presentations. The patient's cousin was the proband (1) and also had the mutation and presented with hemangioblastoma and abnormality of the pancreas.The grandfather (13) was inferred to have the mutation and had a hemangioblastoma. See Figure 2a for family pedigree.

CohortInfo: 20 unrelated VHL families from an ethnically diverse cohort containing both affected and unaffected individuals.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0009711, HP:0005584, HP:0002666, HP:0001732, HP:0000077, HP:0010797 (retinal capillary hemangioma, renal cell carcinoma, pheochromocytoma, abnormality of the pancreas, abnormality of the kidney, hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 31368132

SupplementalData: Supplementary file 1.

Variant: p.F136Lfs*23 (c.408delT)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 43601 https://www.ncbi.nlm.nih.gov/clinvar/variation/43601/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: F136Lfs*23 (c.408delT)

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 5

Case: F, 13Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Positive. The patient's mother (4) also carried this mutation and had a hemangioblastoma. The proband's aunt (5) was confirmed to have the mutation and had VHL presentations. The cousin (8) had the mutation but was asymptomatic. The grandfather (13) was inferred to have the mutation and had a hemangioblastoma. See Figure 2a for family pedigree.

CohortInfo: 20 unrelated VHL families from an ethnically diverse cohort containing both affected and unaffected individuals.

CasePresentingHPOs: HP:0010797, HP:0001732 (hemangioblastoma, abnormality of the pancreas)

CaseHPOFreeText: The patient presented with a hemangioblastoma and abnormality of the pancreas at age 10.

CaseNotHPOs: HP:0009711, HP:0005584, HP:0002666, HP:0000077 (retinal capillary hemangioma, renal cell carcinoma, pheochromocytoma, abnormality of the kidney)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 31368132

SupplementalData: Supplementary file 1.

Variant: p.F136Lfs*23 (c.408delT)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 43601 https://www.ncbi.nlm.nih.gov/clinvar/variation/43601/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: F136Lfs*23 (c.408delT)

MultipleGeneVariants: N/A